UA101608C2 - Method for activation of helper t-cells - Google Patents

Abstract

The invention relates to a method for activation of helper T-cells, comprising stage of peptide WT1 adding to antigen-presenting cells, and by means of this activation of helper T-cells is carried out, where peptide WT1 is able to bind at least two molecules selected from the group: HLA-DRBP1*1501, HLA-DPB1*0901 i HLA-DPB1*0501. The invention also relates to the method for treatment and/or prevention of cancer by activation of helper T-cells.

Description

The field of technology

The present invention relates to a method of activating helper T cells, which includes the addition of the M/T1 peptide to antigen-presenting cells and, with this, the activation of helper T cells, where the M/T1 peptide is able to bind to any of the NO molecules A-OKV171501, molecules NG A-ORV170901 and molecules NI A-ORV170О501, and compositions for this, pharmaceutical compositions for the treatment and/or prevention of cancer by activating helper T cells and similar to them.

Prior art

The UMT1 gene (Wilms tumor gene 1) has been identified as the gene responsible for Wilms tumor, which is a renal cancer in children (non-patent documents 1 and 2). M/T1 is a transcription factor with a zinc finger structure. Initially, the M/T1 gene was thought to be a tumor suppressor gene. However, further stages (non-patent documents 3, 4, 5 and b) showed that the UMMT1i gene rather functions as an oncogene in hematopoietic tumors and solid forms of cancer.

It was shown that T-lymphocytes specific for UMT1 peptide (STI) can be induced by stimulation of peripheral blood mononuclear cells with U/11 peptide, and such STI. damages cancer cells, such as hematopoietic tumor cells and solid cancer cells, which endogenously express M/T1. 100 recognizes the UMT1 peptide in the form of a complex in which the M/11 peptide binds to a class molecule | MNS (major tissue compatibility complex). Therefore, such M/T1 peptide differs depending on the subtypes of class | Ministry of Emergency Situations (patent document 1, non-patent document 7 and patent documents 2, C and 4).

The existence of helper T cells specific for the cancer antigen is important for the effective induction of STI. (non-patent document 8). Helper T-cells are induced and activated by recognizing a complex of MHC class II molecule and an antigenic peptide on antigen-presenting cells. Activated helper T cells produce a cytokine such as I-2, 1-4, 1-5, I/-6, or interferon to promote B-cell growth, differentiation, or maturation. Activated helper T cells function to promote the growth, differentiation, or maturation of other subpopulations of T cells (for example, Tc and TO cells). Thus, T cells have the function of activating the immune system by promoting the growth or activation of B cells or T cells. Therefore, it is considered useful to enhance the function of helper T-cells with the help of an antigenic peptide that binds class I! МНнНо (helper peptide) in cancer immunotherapy, to increase the effect of an anti-cancer vaccine (non-patent document 9). Until now, only the peptide binding to the molecule NI A-OKV170401 (non-patent document 10), the peptide binding to the molecule NI A-OKV170405, and the peptide binding to the molecule NI A-

OKV171502 (patent document 5), were identified as helper peptides. Therefore, there is a need to identify peptides, each of which binds to the molecule NI A-OAB171501, NI A-ORB170901 or NI A-ORB1"0O501.

In addition, it was shown that among the helper peptides, there is a promising helper peptide that can bind to many MHC class II molecules and induce helper T-cells (non-patent documents 11 and 12).

However, it has been very difficult to identify a promising helper peptide that binds to three or more types of MHC class II molecules and provides a sufficient effect.

Patent document 1: UMO 2003/106682

Patent document 2: UMO 2005/095598

Patent document 3: UMO 2007/097358

Patent document 4: international patent application Me PCT/Р2007/074146

Patent document 5: UMO 2005/045027

Non-Patent Document 1: Oapievy! A. Nabeg ei a!., SeiI. 1990 Ucp 29;61(7):1257-69.

Non-Patent Document 2: Sai! KM eiga!., SeiI. 1990 Rer 9;60(3):509-20.

Non-Patent Document 3: Mepke AG egiai., Ipi Kem Suiyu!. 1998;181:151-212. Nehemiah

Non-Patent Document 4: Matadati Tei a!., Viosa. 1996 Arg 1;87(7):2878-84.

Non-Patent Document 5: Ipotse Kei a!., Viosa. 1998 Arg 15;91(8):2969-76.

Non-patent document 6: T5iboi A ei a!., Heshk Kev5. 1999 Mau;23(5):499-505.

Non-patent document 7: OkKa U ei a!., Ittipodepeiis5. 2000 Rer;51(2):99-107.

Non-Patent Document 8: bao Es eiai!., Sapseg Ke5. 2002 Mom 15;62(22):6438-41.

Non-patent document 9: 7epd C, in Ittipoipeg. 2001 Mau;24(3):195-204

Non-patent document 10: Kpidniv A ei ai., Sapseg Ittipoi Ittipoipeg. 2002 9y1I;51(5):271-81.

Non-patent Document 11: Boiigiadoi Kei a!., Vg U Sapseg. 2001 Mom 16;85(10):1527-34.

Non-Patent Document 12: Fuck! UA eiai., In Ittipoi. 2002 di! 1;169(1):557-65

Description of the invention

Problems to be solved by the invention

The problems solved by the invention are: providing a method of activating helper T cells with the UMT71 peptide, which is able to bind to the molecule NIH A-OKV171501, the molecule NIH A-ORV17"0901 or the molecule NHA-ORV1"0О501, and compositions for achieving this, as well as pharmaceutical compositions for the treatment and/or prevention of cancer by activating helper T cells and the like.

Means for solving the specified problems

As a result of intensive research in connection with the situation described above, the applicant discovered that among the M/11 peptides that bind to the NIG A-OKV170405 molecule and the NHA-OKV171502 molecule, the M/11 peptide has the amino acid sequence: Guz Agd Tug Rpe Guz I e!y Zeg Ni Gay SiIp Mei Ni Zeg Ago Guz Ni also binds to the molecule NIH A-OKV171501, molecule NIH A-ORV170901 and molecule NIH A-ORV17"0501. Thus, this invention was created .

The present invention provides: (1) a method of activating helper T cells, which includes adding the M/71 peptide to an antigen-presenting cell and thereby activating helper T cells, where the UM/T1 peptide is able to bind to any which of the NCA-OKV171501 molecule, NCA-ORB170901 molecule and NCA-ORB1"0O501 molecule; (2) the method according to clause (1), where the M/T1 peptide is capable of binding to at least two of the NG A-OAB1"1501 molecule , NSA-ORB170901 molecules and NSA-ORB1"O501 molecules;

(3) the method according to item (1) or (2), where the UMT1 peptide, in addition, is capable of binding to the NHA-OAV170405 molecule or the NIG A-OVAV171502 molecule; (4) the method according to any of paragraphs (1)-(3), where the peptide M/T1 is able to bind at least to the molecule NI A-

OKV171501, molecule NHA-ORV1"0901, molecule NHA-ORV1"0501, molecule NI A-OKV170405 and molecule NHA-OAV171502; (5) the method according to any of paragraphs (1)-(4), where the M/T1 peptide is a peptide containing the amino acid sequence: Guz Agd Tug Rpe Guz Gecy 5eg Ni5 Gay SiIp Mei Ni Zeg Agu Guz Niz (ZEO IO MO: 2); (6) the method according to any of paragraphs (1)-(5), where the addition of the UM/T1 peptide to antigen-presenting cells is carried out by the addition of the M/11 peptide, the addition of an expression vector containing a polynucleotide encoding the peptide

ML, or by adding cells that include an expression vector; (7) a composition for the activation of helper T-cells by adding the peptide UT! to antigen-presenting cells containing the MUT1 peptide, where the M/T1 peptide is capable of binding to any of the NIG A-OAB171501 molecule, the NSA-ORB170901 molecule, and the NSA-ORB1"O501 molecule; (8) a method of treatment or prevention cancer in a subject, which includes adding the M/T1 peptide to antigen-presenting cells and thereby activating helper T cells, where the UMT1 peptide is able to bind to any of the molecule NG A-OKV171501, the molecule NIH A - ОРВ170901 and НСА-ОРВ170501 molecules; (9th pharmaceutical composition for the treatment or prevention of cancer by activating helper T cells by adding the M/T1 peptide to antigen-presenting cells containing the MUT1 peptide, where the U/T1 peptide is able to bind to any which of the molecule NG A-OKV171501, the molecule NIH A-ORB170901 and the molecule NCA-ORB170501; (10) an antibody that specifically binds to the UMT1 peptide, where the M/71 peptide is able to bind to any of the molecules of NHA- OKV171501, NSA-ORB17"0901 molecules and NSA-ORB1"O501 molecules; (11) method of determining the presence or the amount of U/T1 peptide in any of the NG A-OAB171501-positive,

NIHA-ORV170901-positive and NHA-ORV170501-positive subject, including: (a) interaction of anti-MUT1 antibody with a sample from the subject; and (p) determining the presence or amount of anti-M/11 antibody that specifically binds to the U/T1 peptide contained in the sample; (12) a method of treating or preventing cancer, comprising adding the M/T1 peptide to antigen-presenting cells and thereby activating helper T cells, and administering to the subject the activated helper T cells, wherein the MUT1 peptide is capable of bind to the molecule NI A-OKV171501, the molecule NIH A-ORV170901 or the molecule NHA-ORV1"0501; (13) a pharmaceutical composition for the treatment or prevention of cancer containing helper T cells, activated by the addition of peptide M/T1, where the peptide M/ UT1 is able to bind to any of the NIA-

OKV171501, NSA-ORB170901 molecules and NSA-ORB1"O501 molecules; (14) a method of determining the presence or number of M/T1-specific helper T cells in any of NI A-ravB171501-positive, NI A-ORB170901-positive and of an NSA-ORB170501-positive subject, which includes: (a) interaction of a UUT1 peptide complex of an antibody and a molecule of NHA-OKV171501, a molecule of NG A-ORB170901, or a molecule of NHA-ORB170501 with a sample from the subject; and (b) determining the presence or the number of helper T cells that recognize the complex contained in the sample; and (15) a method of determining the presence or number of M/T1-specific helper T cells in NSA-OAV171501-positive, NIH A-YORV1"0901-positive, NHA -YURV1"0501-positive, NIH A-ONAV170405-positive or

NIGA-OAB1"1502-positive subject, comprising: (a) stimulation of peripheral blood mononuclear cells, invasive lymphocytes, tumor cells, cells in ascitic fluid, cells in pleural fluid, cells in cerebrospinal fluid, bone marrow cells, or lymph node cells peptide UMT1; and (p) determining the production of a cytokine or response of helper T cells, where the presence or increase in the amount of produced cytokine or response of helper T cells indicates the presence or number of M/T1-specific helper T cells.

Effects of the invention

The present invention provides a method of activating helper T cells with the peptide UMT1, which binds to the molecule

NIH A-OKV171501, molecule NIHA-ORV17"0901, molecule NIA-ORV17"0501; molecule NIHA-OKV170405 and molecule NI A-OKV171502, and a composition for this, as well as a pharmaceutical composition for the treatment and/or prevention of cancer by activation of helper T cells and the like. Therefore, it is possible to activate ip mimo and ip migo helper T-cells in a subject having any of these MHC class II molecules for the treatment and prevention of cancer. Due to the fact that the 9095 population of Japan is covered by five types of subclasses of MHC class I, helper T cells can be activated for the treatment and/or prevention of cancer in a very wide range of subjects.

A brief description of the figures

In fig. 1 shows a graph representing the amount of IEM produced by TA28.1 cells. In the drawing, the longitudinal axis represents the concentration of IRM-m (pkg/ml). The graphs correspond to "the case of cultivation of peripheral blood mononuclear cells from NHA-OVAB1"1501-positive subject in the absence of M/T1 peptide", "the case of cultivation of TA28.1 cells in the presence of the M/T1 peptide (black bars)", "the case of cultivation peripheral blood mononuclear cells from NHA-OAVI1"1501-positive subject in the absence of M/T1 peptide", "a case of cultivation of peripheral blood mononuclear cells from NHA-OAVI1"1501-negative subject in the presence of UMT1 peptide", respectively, starting left.

In fig. 2 shows a graph representing the number of IEMs, 1-4 and I--10 produced by cells

TA28.1. In the drawing, the longitudinal axis represents the concentration (pkg/ml). The graphs correspond to the values of IEM-

M, 1-4 and 12-10, starting from the left.

In fig. C shows a graph representing the amount of IEM-y, 1--4 and I--10 produced by E15.2 cells.

In the drawing, the longitudinal axis represents the concentration (pkg/ml). The graphs correspond to the values of IEM-y, 1-4 and

And--10, starting from the left.

In fig. 4 shows the production of IEM-m and I--17 NHA-ORV1"0501/"0501-positive mononuclear cells. In the drawing, the horizontal axis represents IEM, and the longitudinal axis represents 1-17. In fig. 4a shows cells without UMT1 peptide stimulation, and in fig. 45 shows the cells stimulated with the peptide

M/11.

In fig. 5 shows a graph representing the growth of TA28.1 T cells. In the drawing, the longitudinal axis represents imp./min. (x10U. The graphs correspond to "the case of co-cultivation of TA28.1 cells with peripheral blood mononuclear cells without pulsatile exposure to the U/T1 peptide", "the case of co-cultivation of TA28.1 cells with peripheral blood mononuclear cells with pulsatile exposure to the MUT7 peptide (black bars)" , "a case of cultivation of TA28.1 cells with peripheral blood mononuclear cells under pulsatile exposure to M/T1 peptide in the presence of an antibody against MHC class", "a case of co-cultivation of TA28.1 cells with peripheral blood mononuclear cells with pulsatile exposure to M/T1 peptide in in the presence of anti-NI A-OK antibodies (shaded bars)", "a case of co-cultivation of TA28.1 cells with peripheral blood mononuclear cells with pulsatile exposure to the UMT peptide! in the presence of anti-NIA-0O antibodies", "a case of co-cultivation of cells

TA28.1 with peripheral blood mononuclear cells with pulsatile exposure to peptide M/11 in the presence of anti-NI A-OR antibody,” starting from the left.

In fig. 6 shows a graph representing the growth of E15.2 T cells. In the drawing, the longitudinal axis represents imp./min. (x10U). Graphs correspond to "a case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells from NHA-ORB1"0901-positive subject without pulsatile peptide exposure

ML1", "a case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells from

NIGA-ORB170901-positive subject with pulsatile exposure to the UMT7 peptide (black bars)", "a case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells from NSA-ORB170901-negative subject without pulsatile exposure to the M/T/1 peptide ", "a case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells from an NHA-ORB1"0901-negative subject with pulsatile exposure to the UUT1 peptide", starting from the left.

In fig. 7 shows a graph representing the growth of E15.2 T cells. In the drawing, the longitudinal axis represents imp./min. The graphs correspond to "the case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells without pulsatile exposure to the UMT1 peptide", "the case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells with pulsatile exposure to the UM/T1 peptide (black bars)", "the case of co-cultivation of E15.2 cells with mononuclear cells of peripheral blood with pulsating influence of MUT peptide! in the presence of antibodies against | MHC class", "case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells with pulsatile exposure to M/T1 peptide in the presence of anti-HA-OK antibody", "case of co-cultivation of E15.2 cells with peripheral blood mononuclear cells with pulsatile exposure by UUT1 peptide in the presence of anti-

NIGA-0O antibodies", and "a case of co-cultivation of E175.2 cells with peripheral blood mononuclear cells with pulsatile exposure to the M/11 peptide in the presence of anti-NI A-OR antibodies (shaded bars)", starting from the left.

In fig. 8 shows a graph representing the growth of NHA-ORB1"0501/"0501-positive mononuclear cells. In the drawing, the horizontal axis represents imp./min. Graphs correspond from left to right "case without stimulation with peptide U/11" and "case with stimulation with peptide U/T1".

In fig. 9 shows that the growth of NSA-ORB1"0501/0501-positive mononuclear cells is suppressed by anti-NIH A-OR antibodies. In the drawing, the horizontal axis represents pulses/min. The graphs correspond from left to right to "the case without stimulation by U/T1 peptide", " a case with stimulation with a control peptide from HIV", "a case with stimulation with a M/T1 peptide", "a case with stimulation with a UMT1 peptide in the presence of an anti-NIH A-OV antibody", "a case with stimulation with a UMT1 peptide in the presence of an anti-NHA-0O antibody ” and “case with stimulation with peptide M/T1 in the presence of anti-NI A-OK antibody”.

In fig. 10 shows a graph that represents the growth of E15.2 T cells in cases of using different concentrations of MUT1 peptide. In the drawing, the longitudinal axis corresponds to imp./min. (x10U, and the horizontal axis represents the concentration of UMT1 peptide.

A preferred way of carrying out the invention

In one aspect, the present invention relates to a method of activating helper T cells comprising adding M/T71 peptide to antigen-presenting cells and thereby activating helper T cells, wherein the peptide

M/T1 is able to bind to any of the NI A-OKV171501 molecule, the NHA-ORV170901 molecule, and the NI A- molecule

ОРВИ1"0501. In the present invention, M/T1 peptide refers to a peptide consisting of part of the amino acid sequence of the human M/UT1 protein shown in ZEO IU MO: 1, a peptide that has a substitution, modification or deletion of one or more amino acids in the amino acid sequence and is able to bind to any of the molecule NG A-OKV171501, the molecule NIH A-ORV170901 and the molecule NIH A-ORV170О501, or a peptide in which various substances, such as an amino acid, a peptide or its analogue can be attached to M -termini and/or C-termini of the peptide.The substance can be processed, for example, by an enzyme in a living organism through a process such as intracellular processing, and finally the M/T1 peptide becomes a form that can bind to any from the NHA-OKV171501 molecule, the NHA-ORV17"0901 molecule and the NHA-ORV1"0501 molecule. The substance can be a substance that modulates the solubility of the M/UTI peptide according to the present invention or increases its stability (protease resistance, etc. ).Alternatively, she may be a substance that specifically delivers the UM/T1 peptide of the present invention, for example, to a given tissue or organ, or increases the efficiency of capture by antigen-presenting cells, or the like. Alternatively, it may be an M/T1 peptide, which is restricted to the same type of MHC class I molecule as in the subject from which the antigen-presenting cells were derived.

Peptide M/T1 according to the present invention is capable of binding to any of the molecules NI A-OKV171501, molecules

NIHA-ORV170901 and NIG A-ORV17"0501 molecules. Thus, the M/T1 peptide can be a peptide that is able to bind to at least two of the NHA-OKV171501 molecule, the NHA-ORV17"0901 molecule and the molecule

NIH A-ORV17"0О501, or a peptide that is able to bind to the molecule NI A-OKV171501 and/or the molecule NI A-

ОРВ170901 and/or molecule NIH A-ОРВ170501, and a molecule of the II class of NGA different from them, for example, a peptide that is able to bind to the molecule NIH A-OKV171501, molecule NIH A-OKV170405 and/or molecule NI A-

OKV171502, a peptide that is able to bind to the molecule NIH A-ORB170901, molecule NIH A-OKV170405 and/or molecule NIH A-OKV170502, peptide that is able to bind to the molecule NIH A-OKV171501, molecule

NIH A-OKV170405 and/or the molecule NIH A-OKV171502, or a peptide that is able to bind to the molecule NI A-

OKV171501, NIA-ORV1"0901 molecule, NIA-ORV1"0501 molecule, NIA-OKV170405 molecule and/or NI A-OKV171502 molecule. Due to the fact that the UT peptide, which has the amino acid sequence: Guz Agd Tug

Rne Huz I ei 5eg Niv I ei Sp Mei Niz Zeg Ago Guz Niv (ZEO IYUO MO: 2) is capable of binding to the NI A- molecule

OKV171501, molecule NIHA-ORV1"0901 and molecule NIA-ORV1"0501, molecule NIHA-0OKV170405 and molecule NHA-OKV171502, the preferred peptide UM/T1 having the following amino acid sequence. In general, a peptide that binds the II class of MHC. Therefore, the UMMT1 peptide preferably has an amino acid sequence consisting of 10-25 amino acids.

Peptide M/71 according to the present invention can be synthesized by methods generally used in this field, or their modifications. Such methods are described, for example, in Reriide Zupipeviv, Ipiegssiepse, Mezhm/

Moscow State University, 1966; Te Rhoivip5, Mo! 2, Asadetis Rgez5 Ips., Memu Moik, 1976; Reriide-Sovvi, Magigep So., Tsa., 1975;

Reriide-Sozei Mo Kizo To dikKep, Magigep So., Tsa., 1985; and Iuakipip Mo Kaipaiza (2oKy), Moi. 14, Reriide-Sovzvi,

NiyukKama - Vook zioge, 1991.

Peptide M/T1 according to the present invention can also be obtained using genetic engineering techniques based on information about the nucleotide sequence that encodes peptide M/11. Such techniques of genetic engineering are well known to those skilled in the art.

Antigen-presenting cells belong to cells, such as dendritic cells, which can present M/T1 peptide together with MHC class II molecule of helper T cells or similar to them. Thus, the subject in which the antigen-presenting cells were obtained must have the same subclass of class II MHC (for example, NG A-

OAVIM1501, NHA-ORV1"0901, NIH A-ORVI1"O501, NI A-OKV170405 or NIA-OKV1"1502) as the one to which the added peptide U/11 binds.

In general, helper T cells are activated by antigen peptide recognition using MHC class II molecule on the surface of antigen-presenting cells by TSC-SOZ complex on the surface of E-cells, and integrin stimulation on the surface of T cells by integrin ligand on the surface of antigen-presenting cells. In the present invention, the activation of helper T cells covers not only the activation of helper T cells, but also the induction and growth of helper T cells. As described above, activated helper T cells function to activate the immune system by increasing the induction, growth, or activation of B cells or T cells. Thus, the method of activation of helper T cells according to the present invention can be used as an adjuvant therapy in the treatment of cancer or similar diseases. Alternatively, helper T cells activated by the method of the present invention can be used for the treatment or prevention of cancer or a similar disease, or can be used as an adjuvant therapy for them. Activation of helpers

T cells can be determined by measuring the amount of cytokine produced or secreted, such as interferon and interleukin and the like.

The addition of the MUT1 peptide to antigen-presenting cells can be carried out directly by adding the M/11 peptide, or indirectly by adding an expression vector containing a polynucleotide encoding the U/T1 peptide, or by adding cells containing an expression vector. An expression vector containing a polynucleotide encoding a peptide

ML and cells containing the expression vector can be obtained by a method well known to a person skilled in the art.

In another aspect, the present invention relates to a composition for activating helper T cells by adding a peptide

M/LT1 to antigen-presenting cells containing the M/T1 peptide, where the M/T1 peptide is capable of binding to any of the NSA-OAVI171501 molecule, the NSA-ORB170901 molecule, and the NSA-ORB1"0501 molecule. When the composition according to this invention is administered OKV171501, NI A-ORV170901 or NIH A-ORV1"0501-positive subject, the immune system of the subject is activated by activation of helper T cells in the subject. The M/T1 gene is expressed at high levels in a variety of cancers and tumors, including hematopoietic tumors such as leukemia, myelodysplastic syndrome, multiple myeloma, or malignant lymphoma, and solid cancers such as gastric cancer, colon cancer, lung cancer, breast cancer, germ cell cancer, liver cancer, skin cancer, bladder cancer, prostate cancer, uterine cancer, cervical cancer, or ovarian cancer. Therefore, the composition according to the present invention can be used as an adjuvant therapy in the treatment or prevention of cancer. Alternatively, helper T-cells activated using the composition according to the present invention can be used, for example, as an adjuvant in the treatment of cancer.

As described above, the M//1 peptide according to the present invention can be a peptide that is able to bind to at least two of the molecule NHA-OKV171501, the molecule NIH A-ORB170901 and the molecule NI A-ORB170501, or a peptide that is able to bind bind to the molecule NI A-OKV171501 and/or the molecule NI A-ORV17"0901 and/or the molecule NIH A-ORV1"0O501, and a molecule of class II MHC, different from them. Thus, as long as antigen-presenting cells are obtained from a subject positive for MHC class I subclass, with which the M/T1 peptide of the present invention can bind, the helper T-cell activation effect of the composition of the present invention can be obtained.

The composition according to the present invention may contain, in addition to the M/T1 peptide, for example, a carrier, excipient, additive or similar ingredient. Due to the fact that the MUT1 peptide contained in the composition according to the present invention activates the helper peptide specifically for the M/T1 peptide, the composition may contain a peptide

ML restricted to MHC class I or can be used with this peptide.

The method of application of the composition according to the present invention can be appropriately selected, depending on such conditions as the desired activation of helper T-cells, the state of the antigen-presenting cell. Examples of such methods include, but are not limited to, intradermal, subcutaneous, intramuscular, intravenous, intranasal, and oral administration, adding antigen-presenting cells to the culture medium. The amount of peptide M/UTT contained in the composition according to the present invention, as well as the form, the number of times of application of the composition according to the present invention, and the like, can be selected accordingly, depending on such conditions as the desired activation of helper T cells, the state of antigen- the presenting cell.

In yet another aspect, the present invention relates to a composition for activating helper T cells by adding the MMT1 peptide to antigen-presenting cells containing an expression vector comprising a polynucleotide encoding the M/T1 peptide, cells containing an expression vector wherein the M peptide /T1 is able to bind to any of the molecule NHA-OKV171501, molecule NHA-ORV1"0901 and molecule NHA-ORV1"0501. The expression vector including the polynucleotide encoding the UMTI peptide and the cells containing the expression vector are described above.

In another aspect, the present invention relates to the use of an expression vector containing a polynucleotide encoding the M/11 peptide and cells containing an expression vector for the preparation of a composition.

In yet another aspect, the present invention relates to a kit for activating helper T cells by adding the UMT1 peptide to antigen-presenting cells containing the UMT1 peptide, wherein the U/T1 peptide is capable of binding to any of the molecule NIH A-OKV171501, NHA-ORVI17"0901 and molecules NHA-ORV1"0501. Preferably, the kit is used in the method of activation of helper T cells. The kit according to the present invention may contain, in addition to the MUT1 peptide, for example, a means for obtaining antigen-presenting cells, a means for determining the activity of helper T cells, or the like. In general, the application guide is attached to the set. By using the kit according to the present invention, it is possible to effectively induce helper T-cells.

In another aspect, the present invention relates to a kit for activating helper T cells by adding a peptide

ML to antigen-presenting cells containing an expression vector including a polynucleotide encoding a peptide

ML, or cells containing an expression vector where the MUT1 peptide is able to bind to any of the molecules

NHA-OKV171501, NSA-ORV170901 molecules and NSA-ORV17"0O501 molecules.

In another aspect, the present invention relates to a method of treating or preventing cancer in a subject, comprising adding the UMT1 peptide to antigen-presenting cells and thereby activating helper T cells, wherein the M/T71 peptide is capable of binding to any -which of the NHA-OKV171501 molecules, NIA molecules-

ОРВ170901 and molecules НГА-ОРВ17"0501. The method according to this invention is a method in which the subject's immune system is activated by activation of helper T cells and the subject is treated or prevented from cancer. Addition of UMT1 peptide to antigen-presenting cells can be carried out directly by adding the M/11 peptide, or indirectly by adding an expression vector containing a polynucleotide encoding the M/11 peptide, or by adding cells containing an expression vector.

As described above, helper T-cells recognize a complex of any of the molecules of the II class of MHC, in particular, the NHA-OKV171501 molecule, the NHA-ORV17"0901 molecule or the NHA-ORV1"0O501 molecule and the UMT1 peptide. Therefore, the subject is a subject that has a class II MHC molecule to which the M/T1 peptide binds, for example, NO A-

OvV171501-positive, NI A-ORV1"0901-positive or NIH A-ORV1"0O501-positive subjects. As described above, the UM/T1 peptide according to the present invention can be a peptide that is able to bind to at least two of the NI A-OKV171501 molecule, the NHA-ORV170901 molecule and the NHA-ORV1"0501 molecule, or a peptide that is able to bind bind to the molecule NIH A-OKV171501 and/or the molecule NIH A-ORB17"0901 and/or the molecule NI A-

ОРВ170501, and a class II NO A molecule different from them. Therefore, in such a case, it is possible to treat or prevent cancer in a subject positive for MHC class I subclass, to which the M/T1 peptide of the present invention can bind. The cancer to be treated or prevented can be any cancer, and examples include hematopoietic tumors such as leukemia, myelodysplastic syndrome, multiple myeloma or malignant lymphoma, and solid cancers such as gastric cancer, colon cancer, lung cancer, breast cancer, germ cell cancer, liver cancer, skin cancer, bladder cancer, prostate cancer, uterine cancer, cervical cancer, or ovarian cancer. In addition, the method according to the present invention can be used with a method of treatment or prevention of cancer with the U/T1 peptide restricted to class I MHC, or a pharmaceutical composition for it.

In another aspect, the present invention relates to a pharmaceutical composition for treating or preventing cancer in a subject by activating helper T cells by adding an M/T1 peptide to an antigen-presenting cell containing a UMT1 peptide, wherein the M/T1 peptide is capable of binding to any - which of the molecules NO A-OKV171501, molecules

NHA-ORV17"0901 and NHA-ORV1"0501 molecules. The U/T1 gene is expressed at high levels in a variety of cancers and tumors, including hematopoietic tumors such as leukemia, myelodysplastic syndrome, multiple myeloma or malignant lymphoma, and solid cancers such as gastric cancer, colon cancer, lung cancer, breast cancer, germ cell cancer, liver cancer, skin cancer, bladder cancer, prostate cancer, uterine cancer, cervical cancer, or ovarian cancer. Therefore, the pharmaceutical composition according to the present invention can be used for the treatment or prevention of cancer.

As described above, the M//1 peptide according to the present invention can be a peptide that is able to bind to at least two of the molecule NHA-OKV171501, the molecule NIH A-ORB170901 and the molecule NI A-ORB170501, or a peptide that is able to bind bind to the molecule NIH A-OKV171501 and/or the molecule NI A-ORV17"0901 and/or the molecule NIH A-ORV17"0501, and the molecule || class NIGA different from them. Thus, as long as the antigen-presenting cells are obtained from a subject positive for MHC class II subclass, to which the UMT1 peptide of the present invention can bind, the pharmaceutical composition of the present invention can be used for the treatment or prevention of cancer.

When the pharmaceutical composition according to the present invention is administered, for example, to a NIHA-YOOAV1"1501-positive, NI A-ORV1"0901-positive and NHA-ORVI1"0501-positive subject, the immune system can be activated by activation of helper T cells by the UMT1 peptide, contained in the pharmaceutical composition, thereby effecting the treatment or prevention of cancer.Thus, the pharmaceutical composition of the present invention can be used together with a method for the treatment or prevention of cancer or with another pharmaceutical composition intended for the same.

The pharmaceutical composition according to the present invention may contain, in addition to the M/T1 peptide as an active ingredient, for example, a carrier, an excipient or similar ingredients. Peptide UMT!, contained in the pharmaceutical composition according to the present invention, binds to the class II MHC molecule on the surface of the antigen-presenting cell and activates helper T-cells. Therefore, the pharmaceutical composition according to the present invention may, in addition, contain an activator, a growth factor, an inducer of helper T-cells or the like, or may contain a U/T1 peptide restricted to class I INO.

The method of administration of the pharmaceutical composition according to the present invention can be appropriately selected, depending on such conditions as the type of disease, the condition of the subject or the target area. Examples of such methods include, but are not limited to, intradermal, subcutaneous, intramuscular, intravenous, intranasal, and oral administration. The amount of peptide contained in the pharmaceutical composition according to the present invention, as well as in the dosage form, the number of times of administration and the like of the pharmaceutical composition according to the present invention can be appropriately selected, depending on conditions such as the type of disease, the condition of the subject or the site -target. One dose of the peptide is usually from 0.0001 mg to 1000 mg, preferably from 0.001 mg to 1000 mg.

In yet another aspect, the present invention relates to a pharmaceutical composition for treating or preventing cancer in a subject by activating helper T cells by adding the M/UT1 peptide to an antigen-presenting cell containing an expression vector comprising a polynucleotide encoding the UMT1 peptide, or a cell containing an expression vector where the M/T1 peptide is capable of binding to any of the molecules of NI A-

OKV171501, NSA-ORV170901 molecules and NSA-ORV1"O501 molecules.

In another aspect, the present invention relates to the use of the UMUT1 peptide, an expression vector containing a polynucleotide encoding the M/T1 peptide, or a cell containing an expression vector for the preparation of a pharmaceutical composition.

In another aspect, the present invention relates to an antibody that specifically binds to the UMUT1 peptide, where the UMUT1 peptide is capable of binding to any of the NHA-OKV171501 molecule, the NHA-ORB170901 molecule, and the NIH A-ORB170501 molecule. The antibody according to the present invention can be obtained by a means or method known to a person skilled in the art. The antibody of the present invention can be used for the diagnosis of various forms of cancer, their prognosis, or the like.

In yet another aspect, the present invention relates to a method for determining the presence or amount of UMT1 peptide in an NHA-OAVI171501-positive, NIH A-ORB17"0901-positive, or NHA-ORB1"0501-positive subject, comprising: (a) interaction of anti - MUT1 antibodies with a sample from the subject; and (p) determining the presence or amount of anti-M/11 antibody that specifically binds to the U/T1 peptide contained in the sample. For example, one can diagnose cancer, its prognosis, or the like by incubating an anti-M/T1 antibody with a sample from a NHA-OAV1"1501-positive, NIHA-YORV1"0901-positive, or NIA-

ARVI1"0501-positive subject, or introduction of anti-M/T1 antibody NHA-OAB1"1501-positive, NO A-

ORV1"0901-positive or NO A-ORV17"0501-positive subject, and determination, for example, of their position, location or number. An anti-M/T1 antibody of the present invention refers to an antibody that specifically recognizes the M/T1 peptide of the present invention. The anti-UUT1 antibody can be a monoclonal antibody or a polyclonal antibody. Anti-M/T1 antibody can be labeled. As a label, a known label such as a fluorescent label or a radioactive label can be used. The presence or amount of UUTT peptide can be easily and quickly determined by its labeling.

In another aspect, the present invention relates to a kit for determining the presence or amount of an M/T1 peptide containing an anti-M/1T1 antibody as an essential component.

In addition, when determining the presence or amount of the U/T1 peptide, when the MU/T1 peptide is able to bind to the NI A-OKV170405 molecule and/or the NI A-OKV171502 molecule, it is possible to determine the presence or amount of the MU/T1 peptide in the subject with such a subclass of the II class of the Ministry of Emergency Situations.

In another aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of cancer containing helper T-cells activated by the U/T1 peptide, where the U/T1 peptide is capable of binding to any of the NHA-OKV171501 molecule, the NHA- ORV17"0901 and NHA-ORV1"0501 molecules. Cancer treatment or prevention is accomplished by induction, growth, or activation of B cells or T cells by activated helper T cells. Thus, the pharmaceutical composition of the present invention in this aspect can be used together with another method of cancer treatment or prevention or with a pharmaceutical composition intended for the same. Activation of helper T cells by the M/T1 peptide includes not only direct activation by the UM/11 peptide, but also indirect activation by an expression vector containing a polynucleotide encoding a UMTI1 peptide or a cell containing an expression vector.

The pharmaceutical composition according to the present invention may contain, in addition to the activated helper cells as an active ingredient, for example, a carrier, an excipient or the like. The method of administration of the pharmaceutical composition according to the present invention can be appropriately selected, depending on such conditions as the type of disease, the condition of the subject or the target area. Examples of such methods include, without limitation, intradermal administration, subcutaneous administration, intramuscular administration, intravenous administration, intranasal administration, and oral administration. The number of helper T-cells contained in the pharmaceutical composition according to the present invention, as well as in the dosage form, the number of times of administration, and the like, of the pharmaceutical composition according to the present invention can be appropriately selected, depending on such conditions as the type of disease, the state of sub object or target area.

In another aspect, the present invention relates to a method of treating or preventing cancer in a subject, comprising adding a UMT1 peptide to an antigen-presenting cell and thereby activating helper

T-cells, and the introduction of activated T-cells into the subject, where the M/T1 peptide is able to bind to any of the NSA-OKV171501 molecule, NHA-ORV170901 molecule and NSA-ORV1"O501 molecule.

In another aspect, the present invention relates to the use of the M/T1 peptide for the preparation of a pharmaceutical composition containing activated T-cells.

In another aspect, the present invention relates to a method for determining the presence or number of UMT1-specific helper T cells in any of NHA-OAB171501-positive, NHA-ORB1"0901-positive and

NIHA-ORB170501-positive subject, which includes: (a) interaction of the UUT1 peptide complex of the antibody and the NHA-OKV171501 molecule, the NG A-ORB170901 molecule or the NHA-ORB170501 molecule with a sample from the subject; and (b) determining the presence or number of helper T cells that recognize the complex contained in the sample. The sample from the subject can be any, as long as there is a possibility that it contains a lymphocyte.

Examples of samples include biological fluids such as blood or lymph and tissue. Peptide complex. M/1 antibody and molecule NHA-OKV171501, molecule NHA-ORV17"0901 or molecule NHA-ORV17"0501 can be obtained, for example, in the form of a tetramer or a pentamer using a method known to a specialist in this field, such as the biotin-streptavidin method . The presence or number of helper T cells recognizing such a complex can be measured using a method known to a person skilled in the art.

In this aspect of the present invention, the complex may be labeled. As a label, a known label such as a fluorescent label or a radioactive label can be used. The presence or amount of UUTT peptide can be easily and quickly determined by its labeling. The method of the present invention in this aspect may be used for cancer diagnosis, prognosis, or the like.

Thus, the present invention also provides a composition for determining the presence or amount of helpers

T cells from any of the NHA-OAV1"1501-positive, NI A-YURV1"0901-positive and NHA-ORV170501-positive subjects, containing the M/T1 antibody peptide complex and NG A-OKV171501 molecules, molecules NO A-

ARVI17"0901 or NHA-ORV1"0O501 molecules.

In addition, the present invention provides a kit for determining the presence or number of helper T cells in any HSA-OAB171501-positive, NI A-ORB170901-positive, and HSA-ORB1"0501-positive subject, which contains a complex of peptide Y /11 antibodies and molecules NHA-OKV171501, molecules NHA-ORV170901 or molecules

NGA-ORV1"0О501.

In addition, when determining the presence or number of helper T cells, when the M/T1 peptide is able to bind to the molecule NI A-OKV170405 and/or the molecule NIH A-OKV171502, when determining the presence or number of helper T cells, it is possible to determine the presence or the number of helper cells in a subject with such a subclass of class II of the MNS. In this case, a complex of peptide U/T1 and molecules of HER class MHC, with which peptide M/1 binds, is used.

In another aspect, the present invention relates to a method of obtaining helper T cells using a complex of the M/T1 peptide and the NSA-OKV171501 molecule, the NHA-ORV170901 molecule or the NHA-ORV170501 molecule, which includes: (a) interaction of the sample with the complex; and (b) obtaining helper T cells that recognize the complex contained in the sample. The complex is described above. The sample can be any sample as long as there is a possibility that it contains a lymphocyte.

Examples of samples include a sample from a subject, such as blood and cell culture. Helper T-cells that recognize the complex can be obtained using a method known to a person skilled in the art, such as EAS5 and MAC5. This invention provides the possibility of cultivating the obtained helper T-cells and using them for the treatment or prevention of various forms of cancer.

Thus, the present invention also relates to helper T cells, which can be obtained by the method of obtaining helper T cells using a complex of the MMT1 peptide and the NHA-OAB1"1501 molecule, the NHA-ORB17"0901 molecule or the NIHA-ORB1"0501 molecule.

In addition, the present invention relates to a kit for obtaining helper T-cells, containing a complex of peptide M/T1 and the molecule NHA-OKV171501, the molecule NIH A-ORV17"0901 or the molecule NHA-ORV170501.

In addition, during the production of helper T cells, when the M/T1 peptide is able to bind to the molecule NI A-

О8170405 and/or the NIG A-OKV171502 molecule, it is possible to obtain helper T-cells that recognize a complex of this subclass of the II class of MHC and the M/T1 peptide. In this case, a complex of the UMTI1 peptide and the MHC II class molecule with which it binds is used.

In another aspect, the present invention relates to a method for determining the presence or number of U/T1-specific helper T cells in any of NHA-OAB171501-positive, NIH A-ORB1"0901-positive and

NIHA-ORV17"0501-positive subject, comprising: (a) stimulation of peripheral blood mononuclear cells, invasive lymphocytes, tumor cells, cells in ascitic fluid, cells in pleural fluid, cells in cerebrospinal fluid, bone marrow cells, or lymph node cells by the UMT1 peptide; and (p) determining the production of a cytokine or helper T cell response, wherein the presence or increase in the cytokine or helper T cell response indicates the presence or number of MUT1-specific helper T cells that recognize the complex contained in the sample Cells such as peripheral blood mononuclear cells, invasive lymphocytes, tumor cells, cells in ascitic fluid, cells in pleural fluid, cells in cerebrospinal fluid, bone marrow cells or lymph node cells used in the method of the present invention can be obtained from a healthy subject or a patient suffering from cancer By using cells from a healthy subject, it is possible to recognize read whether the patient is suffering from cancer or not, whether the subject has a predisposition to it or not, and the like. By using cells from a patient suffering from cancer, it is possible to predict whether immunotherapy using U/T1 in a patient suffering from cancer or the like will have an effect or not. Stimulation of cells with a peptide

ML1 can be carried out by ip miigo or ip mimo. Due to the lightness, the predominant stimulation of the ip migo. The presence of cytokine production or the response of helper T cells, or the amount of cytokines produced or the response of helper cells

T-cells can be determined by a known method.

The following examples illustrate the present invention in more detail, but should not be construed as limiting its scope.

Examples

1. Obtaining antigen-presenting cells

Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood taken from a healthy donor (NHA-OVAB171501-positive, NHA-ORV17"0901-positive or NHA-ORV1"0501-positive). PBMCs were seeded in a b-well plastic plate at a density of 1x107 cells/well in 195 AB serum (Mabi, Miati,

EMU), medium X-MIMO 15 (Saturgeh) and cultured for 2 hours. After cultivation, the suspended cells were removed, and the remaining adherent cells were cultured in 1000 Mod./ml (RergotTesi), 1000 Mod./ml

C2M-C5E (RergoTesi), 1956 AB serum and medium X-MIMO 15. On the 2nd and 4th day, the medium was changed and 1-4 and ZM-S5R were added. On the 6th day, 100 Mod./ml TME-a was added to mature antigen-presenting cells. 2. Induction of CO4-positive T-cells specific for M/T1 peptide

Sra-positive T-cells were isolated from blood obtained from the same donor, using CozeibZer to separate CO4-positive E-cells (bietsSeI). CO4-positive T cells (3x109 cells) were added to each well of a 24-well plate. They were stimulated with autologous antigen-presenting cells (Х105 cells), with an injection of 20 μg/ml of the UUT1 peptide (5EO IO Mo: 2), and exposed to radiation with a dose of 25 Gray. The next day after stimulation, 20 units/ml of 1-2 were added. Similarly, stimulated CO4-positive T cells were stimulated by injection of 20 μg/ml of MUTT peptide every subsequent week. In addition, every subsequent day after the second stimulation, the medium was replaced with medium containing 1-2. CO4-positive T-cells induced by triple stimulation (NSA-OKV171501 and NSA-ORV1"0901-positive

T cells, designated respectively as TA28.1 cells and E15.2 cells, were used for further experiments. 3. IREM measurement

TA28.1 cells and peripheral blood mononuclear cells from the subject from whom the cells were obtained

TA28.1, cultivated in the presence of 20 μg/ml UMT1 peptide μg/ml for 24 hours. After cultivation, the amount of IEM-4 in the supernatant was determined using the EGISA (enzyme-linked immunosorbent assay) kit. As a control, peripheral blood mononuclear cells from an NSA-OAB171501-negative subject were used.

The results are shown in fig. 1. It was confirmed that TA28.1 cells recognize the M/T1 peptide specifically for the NHA-OKV171501 molecule to increase the amount of IEM produced (i.e., activation).

In addition, when using the EGISA kit, it was confirmed that TA28.1 and E15.2 cells do not produce II-4 and 1C-10. The results are shown in fig. 2 and 3. It was confirmed that TA28.1 and E15.2 cells are TI1 cells.

NHA-ORB170501/"0501-positive mononuclear cells were used to perform the following experiments. Cells were suspended in X-MIMO medium (195 AB serum) and 20 μg/ml of peptide was added

M/T1, 10 μg/ml Brefeldin A and 0.5 μg/ml CO28/494. They were incubated at 372°C and 595°C for 4 hours. Cells incubated without the addition of the UUT1 peptide were used as a control. After washing with buffer, anti-COZ-regoR antibody and anti-CO4-ARS antibody were added, and they were incubated at 4"C for 30 minutes. After washing with buffer, cells were fixed and permeabilized using VO Suyuojh/Suioregt (47C, 20 minutes) After washing with the permeabilization buffer buffer VO, anti-IME-y-RITS (VO, clone:

B27) and anti-P-PE (eViozsiepse, clone: eViob40ES17), and they were incubated at 4"C for 30 minutes. After washing with buffer, the cells were analyzed by a laser cell sorter according to their fluorescence intensity

EASZAGgGia. The results are shown in fig. 4. It was confirmed that NHA-ORV1"0501-positive mononuclear cells grow and produce IEM-y and 1-17. 4. Growth analysis

Growth analysis was performed by the INI-thymidine incorporation method. TA28.1 cells (3x107) and peripheral blood mononuclear cells (NSA-OBV171501-positive; 1x105 cells), which were subjected to pulsatile treatment with UMT1 peptide and irradiation, were cultivated in a 96-well plate. After cultivation for 80 hours, 37 kBq/well of INI-thymidine (Ategpat Viozsiepse5) was added. They were incubated for another 16 hours and measured using a DV scintillation counter. Measurement data were presented in the form of impulses/minute (impulses/min.). As a control, peripheral blood mononuclear cells without pulsing treatment were used. In addition, to confirm that the activation signal is specific for the molecule NI A-

OKVI171501, used an antibody against | MHC class, anti-NI A-OK antibody, anti-NI A-0O antibody and anti-

NIGA-OR antibody. The results are shown in fig. 5. It was confirmed that TA28.1 cells were activated by a signal through the UM/T1 peptide and NSA-OKV171501 and showed growth. In addition, it was confirmed that the growth was specific for NG A-OKV171501 because it was suppressed by anti-NI A-OK antibody.

Similarly, E15.2 cells were used to perform growth assays. As an additional control, peripheral blood mononuclear cells from an NSA-ORB1"0901-negative subject were used. The results are shown in Fig. 6 and 7. It was confirmed that E15.2 cells were activated by a signal through the M/11 peptide and NIH A-

ORV170901 and showed growth. In addition, it was confirmed that the growth was specific for NHA-ORB170901 because it was suppressed by the anti-NI A-OR antibody.

In addition, NSA-ORV17"0501/0501-positive mononuclear cells were used to perform a growth assay. As a control, peripheral blood mononuclear cells from an NSA-ORV170501-negative subject were also used. The results are shown in Fig. 8 and 9. It was confirmed , that NI A-YURV170501/70501-positive mononuclear cells were activated by a signal through the peptide UMT1 and NSA-ORB1"0501 and showed growth.

In addition, it was confirmed that the growth was specific for NG A-ORB170O501 because it was suppressed by anti-NI A-OR antibody.

In addition, the analysis of the growth of E15.2 cells was performed with different concentrations of the MUT1 peptide. The concentration of the MUT1 peptide used was 0.08, 0.4, 2, 10, 50, 100 or 150 μg/ml. The results are shown in fig. 10.

It was confirmed that MUT1 peptides stimulate the growth of E15.2 T cells in a concentration-dependent manner.

Industrial applicability

The present invention provides a method of activating helper T-cells with peptide M//1, which is able to bind to the NHA-OKV171501 molecule, the NHA-ORV170901 molecule and the NHA-ORV1"0O501 molecule, and a composition for this, as well as a pharmaceutical composition for the treatment and /or cancer prevention by activating helper T-

cells and similar to them.

Therefore, this invention can be used in the fields of medicine and similar fields, for example, in the fields of development and production of pharmaceutical compositions for the prevention or treatment of various hematopoietic tumors and solid forms of cancer that express the U/T1 gene at a high level.

LIST OF SEQUENCES

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Claims (11)

1. The method of activation of helper T-cells, which includes the addition of the UM/TI peptide to the antigen-presenting cell and, with this help, the activation of helper T-cells, where the M/TI peptide is a peptide selected from (1)-(3) ): (1) a peptide containing the amino acid sequence Mus Ago Tug Rpe Guz G.ei beg Ni I i Sip Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) the peptide according to (1), where the amino acid sequence 5EO AND MO:2 has substitutions, modifications or deletions of one to several amino acids, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence consisting of 25 amino acids or less, and where the peptide M/ TI is able to bind to at least two of: molecules NI.A-RKVI1501, molecules NI.A-YURV170901 1 molecule NIA-YURV1O501. 2. The method according to item I, where the addition of the M/TI peptide to the antigen-presenting cell is carried out by the addition of the U/TI peptide, the addition of an expression vector containing a polynucleotide encoding the UM/TI peptide, or the addition of cells that include an expression vector. 3. Composition for activation of helper T cells by adding the MT peptide to an antigen-presenting cell containing the UM/TI peptide, where the UM/TI peptide is a peptide selected from (1) - (3): (1) a peptide that contains the amino acid sequence Gus Age Tug Re Gus Gey 5eg Niv I ei Sip Mei Niv 5eg Age Mus Niv (5EBO IU MO:2), (2) of the peptide according to (1), where the amino acid sequence 5E0OO I MO:2 has substitutions, modifications or deletion of one to several amino acids, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence that consists of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: molecules NI.A- RKVI121501, molecules NHA-YURV 170901 1 molecules NIA-YURV 120501. 4. The method of treatment or prevention of cancer in a subject who is any of NI A-OKVI1501-positive, NILA-URVI"0901-positive and NILA-YURV170501-positive subject, which includes the addition of the U/TI peptide to the antigen -presenting cell 1, with the help of this, activation of helper T-cells, where the UM/TI peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Guz Ago Tug Rpe Guz G. ей бег Ни И и СИП Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) peptide according to (1), where the amino acid sequence 5EO I MO:2 has substitutions, modifications or deletions from one to several amino acids, 1 (3) the peptide according to (1) or (2), where the peptide has an amino acid sequence that consists of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: molecules NI.A- RKVI121501, molecules NGA-YURV 170901 1 molecule NIA-YURV 120501. 5. Pharmaceutical composition for the treatment or prevention of cancer in a subject who is any of NIHA-YUKVI151501-positive, NILA-URVI0O901-positive 1 NHA-ORVI"O501-positive subject, by activation of helper T cells by adding a peptide M/TI to an antigen-presenting cell containing the M/T I peptide, where the M/TI peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Gus Age Tug Re Gus Gey 5eg Niv I i Sip Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) peptide according to (1), where the amino acid sequence 5EO I MO:2 has substitutions, modifications or deletions from one to several amino acids, 1 (3) the peptide according to (1) or (2), where the peptide has an amino acid sequence that consists of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: molecules NI.A- RKVI151501, molecules NIA-YURV170901 1 molecule NIA-YURV1O501. 6. An antibody that specifically binds to the M/TI peptide, where the M/TI1 peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Gus Age Tug Re Gus Gei 5eg Niv I and Sip Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) the peptide according to (1), where the amino acid sequence 5EO I MO: 2 has substitutions, modifications or deletions of one to several amino acids, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence consisting of 25 amino acids or less, and where the M/TI peptide is capable of bind to at least two of: molecule NI.A-RKVI121501, molecule NHA-YURV 170901 1 molecule NIA-YURV 120501. 7. Method for determining the presence or quantity of the MTI peptide in any of the NIGA-OKVIx1501-positive, NILA-YURVI"0901-positive and NILA-YURV170501-positive subjects, where the M/TI peptide is a peptide selected from (1 )-(3): (1) a peptide containing the amino acid sequence Mus Age Tug Rrbe Gus I ep 5eg Niv I ey SiP Mei Niv 5eg Age Mus Niv (5EBO IYU MO:2), (2) peptide according to (1), where the amino acid sequence 5EO AND MO:2 has one to several amino acid substitutions, modifications or deletions, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence that consists of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: NI.A-RKVI121501 molecule, NIA-YURV 170901 molecule, and NIA-YURV12O501 molecule, and the method includes: (a) interaction of an anti-M/TI1 antibody, which specifically binds binds to the M/TI peptide, 13 a sample from a subject who is any of NILA-YUKV11501-positive, NIA-YURV120901-positive AND NIA-YURV170501-positive subject, 1 (5) will determine detection of the presence or amount of anti-M/TI antibody that specifically binds to the M/T I peptide contained in the sample. 8. A method of treating or preventing cancer, comprising adding an MTI peptide to an antigen-presenting cell and thereby activating helper T cells, 1 administration to a subject who is any of the NIA-YUKVI"1501-positive, NIA-YURV170901-positive and NIA-YURV120501-positive subject, activated helper T-cells, where the M/TI peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Guz Age Tug Re Guz Gey 5eg Niv I and SIP Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) of the peptide according to (1), where the amino acid sequence 5EO I MO:2 has substitutions, modifications or deletions from one to of several amino acids, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence consisting of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: NO.A molecules - RKVI121501, NGA-YURV molecules 170901 1 NIA-YURV 120501 molecules. 9. A pharmaceutical composition for the treatment or prevention of cancer in a subject who is any one of NIA-YUKVI151501-positive, NILA-YURVI0O901-positive 1 NHA- ARVI"O501-positive subject, containing helper T cells, activated by the addition of the M/TI peptide, where the M/TI peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Mus Age Tug Re Gus Gey 5eg Niv I ei Sip Mei Niv 5eg Age Muz Niv (5EBO IU MO:2), (2) peptide according to (1), where the amino acid sequence of 5EO I MO:2 has substitutions, modifications or deletions from one to several amino acids, 1 (3) peptide according to (1) or ( 2), where the peptide has an amino acid sequence consisting of 25 amino acids or less, and where the M/TI peptide is capable of binding to at least two of: molecules NI.A- RKVI121501, molecules NHA-YURV 170901 1 molecules NIA-YURV 120501 . 10. The method of determining the presence or number of UT I-specific helper T-cells in a subject who is any of NIA-YUKVI"1501-positive, NIA-YURV170901-positive and NIA-YURV170501-positive subject that includes: (a) the interaction of the MTI peptide complex and the NIA-YUOKV1I121501 molecule, the NIA-ORVI"0901 molecule or the NIA-YURVI"O501 molecule with 13 samples from the subject; where the M/TI peptide is a peptide selected from (1)-(3): (1) a peptide containing the amino acid sequence Gus Age Tug Re Gus Gei 5eg Niv I and Siip Mei Niv 5eg Age Mus Niv (560 IU MO: 2), (2) of the peptide according to (1), where the amino acid sequence 5EO I MO:2 has substitutions, modifications or deletions from one to several amino acids, 1 (3) of the peptide according to (1) or (2), where the peptide has the amino acid a sequence that consists of 25 amino acids or less, and where the M/TI peptide is able to bind to at least two of: molecules NIA-REVI121501, molecules NGA-YURV 170901 1 molecules NI A-YURV 120501, 1 (5) determination of the presence or number of helper T cells recognizing the complex contained in the sample. 11. The method of determining the presence or number of UT I-specific helper T cells in a subject who is any of NIA-YUKVI"1501-positive, NIA-YURV170901-positive and NIA-YUKV170501-positive subject, which includes: (a) stimulation of peripheral blood mononuclear cells, invasive lymphocytes, tumor cells, cells in ascitic fluid, cells in pleural fluid, cells in cerebrospinal fluid, bone marrow cells or lymph node cells with an MTI peptide, where the M/T 1 peptide is a peptide , selected from (1)-(3): (1) a peptide containing the amino acid sequence Guz Ago Tug Rpe Guz G.ey beg Ni I i Sip Mei Niv 5eg Age Mus Niv (560 IU MO:2), (2) peptide according to (1), where the amino acid sequence 5EO AND MO:2 has substitutions, modifications or deletions from one to several amino acids, 1 (3) peptide according to (1) or (2), where the peptide has an amino acid sequence that consists of 25 of amino acids or less, and where the peptide M/TI is able to bind to at least two of: molecule NI.A-REVI121501, mo molecules NHA-YURV 170901 1 molecules NIA-YURV 170501, 1 (5) determination of cytokine production or response of helper T cells, where the presence or increase in the amount of produced cytokine or response of helper T cells indicates the presence or number of MT 1-specific helper T cells - cells